1. Field of the Invention
The present invention relates to a method for detecting risk of Alzheimer's disease by using immunomagnetic reduction (IMR) assays of the product of the concentrations of tau protein and Aβ-42 protein, two biomarkers for Alzheimer's disease.
2. Description of Prior Art
Due to rapid aging of the global population, neurodegenerative diseases become serious problems nowadays. Dementia is the most prevalent neurodegenerative disease among them all. In most regions of the world the prevalence rate of dementia among the elderly over the age of 60 is 5-7%. It was projected that close to 35.6 million people worldwide would suffer from dementia in 2010. The World Health Organization has urged that all governments, policy-makers and other stakeholders should view the impact of dementia as an increasing threat and should allocate all necessary resources to make medical and social care systems ready for the imminent threat of dementia.
Patients with Alzheimer's disease (AD) comprise 50%-70% of the elderly population suffering from dementia. Neuroimaging and neurocognitive tests are two cornerstones of the current medical practice used to diagnose Alzheimer's disease. Although neurocognitive tests are easier to implement as compared to neuroimaging, the results depend not only on the degree of neurodegeneration but also on other factors such as education, cultural background, social economic status, etc. Hence, care must be taken when patients are assessed by neurocognitive tests and the test results should not be the only information to reach a final diagnosis of Alzheimer's disease. As for neuroimaging, structural or functional data can be obtained to diagnose Alzheimer's disease on an objective ground. For example, hippocampal atrophy can be identified either qualitatively (visual rating) or quantitatively (volumetry) by using magnetic resonance imaging; and amyloid or tau positron emission tomography (PET) can show amyloid plaques and neurofibrillary tangles typically found in the brains of Alzheimer's disease patients. However, neuroimaging is expensive and generally not accessible, especially in private clinics or small hospitals. Therefore, people are motivated to develop other technologies for diagnosing Alzheimer's disease.
Molecular diagnosis is the new trend of in-vitro diagnosis of Alzheimer's disease. The potential biomarkers include amyloids, tau protein, and their derivates. Most of these biomarkers are found in cerebrospinal fluid (CSF). Lumbar puncture is necessary in order to collect CSF samples. Since the CSF sampling process is relatively risky and discomfort, CSF samples are not suitable for screening Alzheimer's disease on a large scale, nor are they suitable for monitoring of disease prognosis or therapeutic effect on a long term basis which requires repetitive samplings. Therefore, biomarkers in body fluids other than CSF have been sought. One of the most promising body fluids is blood which the most reliable, convenient and familiar clinical sample. However, the concentrations of biomarkers in blood are very low, so low that they are expressed at the level of pg/ml. Ultra-high-sensitivity assay technologies are needed for the detection of these ultra-low-concentration biomarkers.
An ultra-high-sensitivity technology for immunoassay had been developed in 2008. This technology is now referred to as superconducting quantum interference device (SQUID) immunomagnetic reduction (IMR) assays. The low-detection limits of the SQUID based IMR for amyloids and tau protein were found to be 1-10 pg/ml, which made the measurement of plasma biomarkers for diagnosing Alzheimer's disease possible. Hence, the present invention discloses the characterizations of SQUID IMR for assaying biomarkers in human plasma.